Solvent-induced phase separation enhances the drug loading and encapsulation efficiency of a highly hydrophilic low-molecular-weight S-propargyl-cysteine in injectable PLGA microspheres

Efficient encapsulating of highly hydrophilic low-molecular-weight compound within poly (D, L-lactic-co-glycolic acid) (PLGA) to obtain microspheres with both excellent drug loading capacity (DL) and encapsulation efficiency (EE) was substantially challenging. This study specifically aimed to enhance both the DL and EE of this hydrophilic low-molecular-weight compound S-propargyl-cysteine (SPRC) while extending its release duration through implementation of the solvent-induced phase separation (SIPS) methodology. S-propargyl-cysteine (SPRC)-loaded PLGA microspheres (SP-MSs) were fabricated using conventional emulsion solvent evaporation techniques (W/O/W and S/O/W) and compared with those prepared via SIPS. The influences of various preparation techniques on critical pharmaceutical properties of sustained-release SP-MSs, including drug loading capacity, encapsulation efficiency, in vitro release profiles, surface-localized drug content, crystal state of SPRC, and microstructural characteristics were also systematically investigated. Microspheres sythesized through SIPS demonstrated a remarkable enhancement in DL, increasing from 0.90% to 9.91%, with the corresponding EE improving dramatically from 17.8% to 99.2%. Furthermore, the SIPS approach effectively mitigated the initial burst release phenomenon commonly observed in polymeric microsphere formulations. In vivo pharmacokinetic studies in Sprague-Dawley rats confirmed the sustained-release profile of the optimized formulation, maintaining stable plasma concentrations for an extended period of seven days. These findings establish SIPS as a superior methodology for encapsulating SPRC within PLGA microspheres, effectively addressing dual challenges of low DL and EE. This investigation provides significant methodological insights for the effective encapsulation of hydrophilic low-molecular-weight therapeutic agents within PLGA-based delivery systems, offering a promising strategy for achieving prolonged sustained-release both in vitro and in vivo . Solvent-induced phase separation was employed to encapsulate highly hydrophilic S-propargyl-cysteine (SPRC) within injectable PLGA microspheres to (i) maximize EE and DL, (ii) suppress the initial burst, and (iii) achieve prolonged, controlled release of SPRC for 7 days both in vitro and in vivo . Download: Download high-res image (93KB) Download: Download full-size image